Compositions and methods for alleviating impaired mental function, memory loss and reducing recovery time in anaesthetized mammals

Abstract

Composition and methods of alleviating impaired mental function and memory loss in mammals and reducing the recovery time from anaesthesia in age mammals, comprising treating the mammal with a non-toxic, enhancing effective amount of a cell membrane permeant calcium buffer. The buffer is preferably a calcium ion chelating agent having a KD selected from the range 1x10-4 to 1x10-8 Molar and being essentially calcium ion-selective over other metal ions. A most preferred buffer is BAPTA-AM.

Description

This invention relates to methods of alleviating impaired mental function, memory loss and reducing recovery time in anaesthetized mammals using a cell membrane permeant calcium buffer, said calcium buffers per se, pharmaceutical compositions comprising said calcium buffers and methods for the preparation of said pharmaceutical compositions.Progressive learning and memory impairment occurs during the normal course of aging (1,2,3). A strong functional link has been established between the hippocampal region of the brain and learning and memory of spatial information (4,5,6). Also, age-related changes in neuroanatomical, neurochemical and neurophysiological parameters of this structure of the brain have been well documented and causally linked to the etiology of memory impairment (5,7,8). This age-dependent impairment of spatial learning is strongly correlated with a deficit in the maintenance of neuronal activity long-term potentiation (LTP) in the hippocampus (9). LTP, a form of sy...

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Benefits of technology

The dysfunction in calcium homeostasis in brain neurons is thought to be one of the contributing factors to cognitive dysfunction in senescent humans and animals Aged rats show impairment in their cognitive abilities and increased calcium level in the specific hippocampus and cortex regions of their brain. We have found that in vivo treatment with the cell permeant calcium buffer, bis (O-aminophenoxy)-ethane-N,N,N,N-tetraacetic acid--acetoxymethyl ester (BAPTA-AM) affected the spatial memory of rats. Aged (22 months old) Fisher 344 rats were trained in a hidden platform version of a water maze constituting a hippocampally dependent learning task. The results showed that: (a) adminstration of BAPTA-AM (5 mg/kg) before each training session significantly improved rats' performance in the water maze; b) the improvement was mostly visible within the first 4-5 days of 8 days training; (c) all rats showed comparable performance at the end of training, but the controls never achieved better scores than BAPTA rats; and (d) a retention test carried out 35 days after the last BAPTA-AM injection revealed long lasting tendency of positi

Problems solved by technology

Accordingly, the age-dependent decrease in anaesthetic requirement is probably due to incr

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